Aberrant functional and causal connectivity of the amygdala in herpes zoster and post-herpetic neuralgia patients

Abstract

Objective: Resting-state functional magnetic resonance imaging (rs-fMRI) and Granger causality analysis (GCA) were used to observe the characteristics of amygdala and whole-brain effect connections in patients with herpes zoster (HZ) and post-herpetic neuralgia (PHN) and to determine their relationship with clinical features.

Methods: Rs-fMRI scans were performed on 50 HZ; 50 PHN; and 50 age-, sex- and education-year-matched healthy controls (HCs). Bilateral amygdala subregions were used as seeds for functional connectivity (FC). GCA was used to analyze the effective connection of brain regions that were significantly different among groups. Then, the correlation between FC, and GCA values and clinical indices was investigated.

Results: PHN had impaired FC between the amygdala subregion with the putamen, cortex, anterior cingulate cortex (ACC) to HCs and reduced FC of medial amygdala (MeA) with the parieto-occipital lobe and motor cortex to HZ; HZ had reduced FC of the lateral amygdala (LA) with the insula to HCs. GCA values from the bilateral LA to the bilateral ACC, left MeA to the bilateral ACC and left putamen, and right ACC to the bilateral MeA were reduced in PHN patients compared to HCs. Compared with HCs, the GCA values from the left MeA to the left ACC and right putamen were reduced in HZ. The GCA values from the amygdala subregion to the ACC were positively correlated with HAMA or HAMD scores in PHN.

Conclusion: PHN showed reduced FC between the amygdala subregions and cortico-putamen and decreased effective connectivity from the amygdala subregion to the ACC and putamen.

Advances in knowledge: HZ and PHN patients had significant changes in effective connectivity in brain regions, including diverse functional areas emanating from and projecting to the amygdala. The current findings will provide a new perspective for understanding the neuropathophysiological mechanism HZ and PHN.

Figure 1.

Seed points correspond to the analysis of the connectivity of the four subregions of the amygdala.

Figure 2.

Brain regions with significant differences in FC among HC, HZ and PHN patient groups using the medial and lateral amygdala as seed points. l, left hemisphere; r, right hemisphere. GRF corrected, p < 0.001 for voxel level, p < 0.05 for cluster level, two-tailed. FC, functional connectivity; GRF, Gaussian random field; HC, healthy control; HZ, herpes zoster; PHN, post-herpetic neuralgia.

Figure 3.

Schematic diagrams of effect connections among the PHN, HZ, and HCs groups shown by GCA: (a) Bilateral lateral amygdala to bilateral ACC GCA values were reduced in the PHN group compared with the HC group. (b–e) Violin diagrams showing the distribution of GCA values among the three groups; (f–h) The correlations between abnormal GCA value and clinically relevant variables in PHN patients. ACC, anterior cingulate cortex; FC, functional connectivity; GCA, Granger causality analysis; GRF, Gaussian random field; HC, healthy control; HZ, herpes zoster; PHN, post-herpetic neuralgia.

Figure 4.

(a) Schematic diagrams of GCA connections between the right medial amygdala to bilateral ACC and the right PUT (arrows represent reduced effect connections). (b–d). Violin diagrams showing GCA values among the three groups. (e-g) The correlations between abnormal GCA value and clinically relevant variables in PHN patients. ACC, anterior cingulate cortex; GCA, Granger causality analysis; PHN, post-herpetic neuralgia.

Figure 5.

(a) Schematic diagram of effect connections among the three groups of brain regions PHN, HZ, and HC shown by GCA (arrows represent diminished effect connections from the right ACC to the bilateral medial amygdala, respectively); (b-c) violin plot showing GCA values among the three groups. (d) The correlations between GCA value and clinically relevant variables in HZ patients. ACC, anterior cingulate cortex; FC, functional connectivity; GCA, Granger causality analysis; HC, healthy control; HZ, herpes zoster; PHN, post-herpetic neuralgia.